IL-15 activates telomerase, minimizes telomere loss, and may preserve the replicative lifespan of memory CD8+ T cells: One of the central issues of immunological memory is how memory cells are maintained over long periods of time in vivo without loss of their replicative capacity. Memory lymphocytes are derived from naive lymphocytes after the interaction with antigen, and are long lived. The maintenance of memory lymphocytes appear to be dependent on cytokines such as IL-2, IL-7, and IL-15. IL-15 is capable of promoting proliferation and long-term survival of memory CD8+ T cells in an antigen independent fashion. While IL-15 plays a key role in the homeostasis of memory CD8+ T cells, it is unknown whether IL-15 regulates the replicative lifespan of memory CD8+ T cells. Here, we have demonstrated that IL-15 is capable of inducing telomerase activity through activation of Jak3 and PI3-K/AKT signaling pathways in memory phenotype CD8+ T cells. Furthermore, IL-15 induced telomerase activity is associated with the relative stable telomere length in long term cultured memory phenotype CD8+ T cells. Previous reports showed that exogenous expression of telomerase catalytic unit (hTERT) prevents telomere loss and extends their replicative lifespan of CD8+ and CD4+ T cells, suggesting that preservation of telomere structure can extend cellular replicative lifespan of T cells. By activating and maintaining telomerase activity in memory CD8+ T cells, IL-15 may preserve the replicative lifespan of dividing memory CD8+ T cells.